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Salix and Pharming Announce FDA Approval of RUCONEST® for the Treatment of Acute Angioedema Attacks in Patients with Hereditary Angioedema (HAE)

RALEIGH, N.C. & LEIDEN, The Netherlands --(Business Wire)--

Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) and Pharming Group NV (
EURONEXT: PHARM) today announced that the Food and Drug Administration
has approved RUCONEST® (C1 Esterase Inhibitor [Recombinant])
50 IU/kg for the treatment of acute angioedema attacks in adult and
adolescent patients with hereditary angioedema (HAE). Because of the
limited number of patients with laryngeal attacks, effectiveness was not
established in HAE patients with laryngeal attacks.

"We are pleased that RUCONEST® provides the HAE community
with another FDA-approved option for treating painful and debilitating
HAE attacks," said Anthony Castaldo, President of the Hereditary
Angioedema Association (US HAEA), a non-profit patient services and
research organization with a membership of over 5,000 HAE patients in
the United States.

RUCONEST® is a recombinant C1 esterase inhibitor that can be
administered by the patient after receiving training by a healthcare
provider. HAE attacks stem from a deficiency of the C1 inhibitor protein
in the blood. HAE is a rare inherited genetic condition that is often
not properly diagnosed until later in a patient's life as the symptoms
of an attack can mirror someone experiencing an allergic reaction.
Severe, painful swelling can occur at any time, which means most people
suffering from HAE deal with the constant fear of when their next attack
might surface and how that might impair their lives and those around
them.

"Results in the pivotal clinical trial demonstrate RUCONEST®
is a safe and effective option for the treatment of acute hereditary
angioedema attacks," said Dr. Marc Riedl of the US HAEA Angioedema
Center at the University of California - San Diego and primary
investigator of the phase III study. "At the US HAEA Angioedema Center,
we strive to better the lives of those suffering from hereditary
angioedema and part of that is ensuring patients have access to advanced
treatments that have been proven to work in clinical trials. RUCONEST is
an important addition to those treatment options."

Sijmen de Vries, CEO of Pharming, said: "The approval of RUCONEST® in
the US is a very significant milestone for Pharming. For many years we
have strived to make RUCONEST® - the first recombinant replacement
therapy for C1Inhibitor deficiency - available to the HAE patient
community in the US, because we were aware of the great value and
benefit this product adds to patients' lives. Today we are proud to have
achieved this goal in the US."

"RUCONEST® is a much needed treatment option for patients
suffering from acute attacks of hereditary angioedema. Until now, there
hasn't been an FDA approved recombinant C1 esterase inhibitor option to
treat symptoms of HAE," said Carolyn J. Logan, President and Chief
Executive Officer of Salix. "The unpredictability of HAE can make
patients feel uncertain about when their next attack might strike, which
is why it is important to have a medicine that can be administered by
the patient that resolves an attack. Salix is proud to make RUCONEST®
available."

The FDA approval of the Biologics License Application (BLA) for RUCONEST®
for treatment of acute angioedema attacks in patients with HAE is based
on a randomized, double-blind, placebo-controlled, phase III trial (RCT)
which included an open-label extension (OLE) phase and is supported by
the results of two additional RCTs and two additional OLE studies. The
pivotal RCT and OLE studies analyzed the results from 44 subjects who
experienced 170 HAE attacks. The primary efficacy endpoint was the time
to beginning of symptom relief, assessed using patient-reported
responses to two questions about the change in overall severity of their
HAE attack symptoms after the start of treatment. These were assessed at
regular time points for each of the affected anatomical locations for up
to 24 hours. To achieve the primary endpoint, a patient had to have a
positive response to both questions along with persistence of
improvement at the next assessment time (i.e., the same or better
response).

A statistically significant difference in the time to beginning of
symptom relief was observed in the intent-to-treat population (n=75)
between RUCONEST and placebo (p=0.031, log-rank test); the median time
to beginning of symptom relief was 90 minutes for RUCONEST patients
(n=44) and 152 minutes for placebo patients (n=31).

RUCONEST® is manufactured by Pharming Group NV in the
Netherlands. Salix has licensed exclusive rights from Pharming to
commercialize RUCONEST® in North America and market RUCONEST®
for the treatment of acute HAE attack symptoms.

Salix currently plans on making RUCONEST® accessible to
patients later in 2014.

Indication:

RUCONEST® is a C1 esterase inhibitor [recombinant] indicated for the
treatment of acute attacks in adult and adolescent patients with
hereditary angioedema (HAE). Effectiveness was not established in HAE
patients with laryngeal attacks.

Important Safety Information:

RUCONEST ® (C1 esterase inhibitor [recombinant]) is contraindicated in
patients with a history of allergy to rabbits or rabbit-derived
products, and patients with a history of life-threatening immediate
hypersensitivity reactions to C1 esterase inhibitor preparations,
including anaphylaxis.

Severe hypersensitivity reactions may occur. The signs and symptoms of
hypersensitivity reactions may include hives, generalized urticaria,
tightness of the chest, wheezing, hypotension, and/or anaphylaxis during
or after injection of RUCONEST. Should symptoms occur, discontinue
RUCONEST nd administer appropriate treatment. Because hypersensitivity
reactions may have symptoms similar to HAE attacks, treatment methods
should be carefully considered.

Serious arterial and venous thromboembolic (TE) events have been
reported at the recommended dose of plasma derived C1 esterase inhibitor
products in patients with risk factors. Risk factors may include the
presence of an indwelling venous catheter/access device, prior history
of thrombosis, underlying atherosclerosis, use of oral contraceptives or
certain androgens, morbid obesity, and immobility. Monitor patients with
known risk factors for TE events during and after RUCONEST
administration.

RUCONEST has not been studied in pregnant women; therefore, should only
be used during pregnancy if clearly needed.

The most common adverse reactions (incidence =2%) were headache, nausea,
and diarrhea. The serious adverse reaction in clinical studies of
RUCONEST was anaphylaxis.

Please see complete Prescribing Information for RUCONEST.

About RUCONEST®

RUCONEST® (C1 Esterase Inhibitor [Recombinant]) 50 IU/kgis
an injectable medicine that is used to treat acute angioedema attacks in
adult and adolescent patients with hereditary angioedema(HAE).
HAE is caused by a deficiency of the C1 esterase inhibitor protein,
which is present in blood and helps control inflammation (swelling) and
parts of the immune system. A shortage of C1 esterase inhibitor can lead
to repeated attacks of swelling, pain in the abdomen, difficulty
breathing and other symptoms. RUCONEST® contains C1 esterase
inhibitor at 50 IU/kg.

When administered at the onset of HAE attack symptoms at the recommended
dose, RUCONEST® works to return a patient's C1-INH levels to
normal range and quickly relieve the symptoms of an HAE attack with a
low recurrence of symptoms.

RUCONEST® is the first and only plasma-free, recombinant
C1-INH approval from the U.S. Food and Drug Administration (FDA) and was
approved in July 2014.

About HAE

RUCONEST has been granted Orphan Drug designation by the FDA for the
treatment of acute angioedema attacks in patients with hereditary
angioedema (HAE).With RUCONEST now approved by the FDA, Salix
believes this designation should provide seven years of marketing
exclusivity in the United States.

Hereditary angioedema (HAE) is a genetic condition occurring between 1
in 10,000 to 1 in 50,000 people. Those with HAE experience episodes of
swelling in their extremities, face and abdomen, with potentially
life-threatening swelling of the airway. When it occurs in the abdomen,
this swelling can be accompanied by bouts of nausea, vomiting and severe
pain. Swelling in the face or extremities can be painful, disfiguring,
and disabling.

HAE patients have a defect in the gene that controls production of a
protein found in the blood vessels, called C1 inhibitor or C1-INH. When
a person's C1-INH levels are low, fluid from blood vessels can leak into
nearby connective tissues, causing severe pain and swelling and, in rare
cases, death from asphyxiation from airway swelling.

About Pharming Group NV

Pharming Group NV is developing innovative products for the treatment of
unmet medical needs. RUCONEST® (conestat alfa) is a recombinant human C1
esterase inhibitor approved for the treatment of angioedema attacks in
patients with HAE in the USA, Israel, all 27 EU countries plus Norway,
Iceland and Liechtenstein. RUCONEST® is distributed in the EU by Swedish
Orphan Biovitrum. RUCONEST® is partnered with Salix Pharmaceuticals Inc.
(NASDAQ: SLXP) in North America. The product is also being evaluated for
various follow-on indications. Pharming has a unique GMP compliant,
validated platform for the production of recombinant human proteins that
has proven capable of producing industrial volumes of high quality
recombinant human protein in a more economical way compared to current
cell based technologies. In July 2013, the platform was partnered with
Shanghai Institute for Pharmaceutical Industry (SIPI), a Sinopharm
Company, for joint global development of new products. Pre- clinical
development and manufacturing will take place at SIPI and are funded by
SIPI. Pharming and SIPI initially plan to utilize this platform for the
development of rhFVIII for the treatment of Haemophilia A. Additional
information is available on the Pharming website; www.pharming.com.

About Salix Pharmaceuticals

Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina,
develops and markets prescription pharmaceutical products and medical
devices for the prevention and treatment of gastrointestinal diseases.
Salix's strategy is to in-license late-stage or marketed proprietary
therapeutic products, complete any required development and regulatory
submission of these products, and commercialize them through the
Company's 500-member specialty sales force.

For full prescribing information and important safety information on
Salix products, including BOXED WARNINGS for OSMOPREP, AZASAN, GLUMETZA
and METOZOLV, please visit www.salix.com where
the Company promptly posts press releases, SEC (News - Alert) filings and other
important information or contact the Company at 919 862-1000.

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Salix Disclosure Notice

As previously announced on July 8, 2014, Salix, Cosmo Pharmaceuticals
S.p.A. and Irish domiciled Cosmo Technologies Limited entered into an
Agreement and Plan of Merger and Reorganization, pursuant to which a
subsidiary of Cosmo Technologies Limited will merge with and into Salix,
with Salix as the surviving entity, and Salix will become an indirect,
wholly-owned subsidiary of Cosmo Technologies Limited, which will change
its name to Salix Pharmaceuticals, plc.

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